Optimized bio-synchronous bioactive agent delivery system

ABSTRACT

Optimized bio-synchronous drug delivery begins with establishing a bio-synchronous treatment protocol that incorporates individual temporal and innate biological characteristics into a pharmacological treatment plan. The bio-synchronous treatment protocol is thereafter initiated using bioactive agent delivery device. Bio-synchronous drug delivery includes continual collection of patient data such as physical, psychological, temporal and environmental characteristics. This data is analyzed so to not only determine an initial treatment protocol but to also determining whether modification to the ongoing bio-synchronous treatment protocol is required. And, responsive to determining a modification is required the system modifies the bio-synchronous treatment protocol and use of delivery device. These modifications and treatment protocols can include reactive and proactive psychological support supplied to the patient in a variety of formats.

RELATED APPLICATION

The present application relates to and claims the benefit of priority toU.S. Provisional Patent Application no. 61/756,339 filed 24 Jan., 2013entitled Optimized Biosynchronous Transdermal Drug Delivery, which ishereby incorporated by reference in its entirety for all purposes as iffully set forth herein.

BACKGROUND OF THE INVENTION

1. Field of the Invention

Embodiments of the present invention relate, in general, tobio-synchronous bioactive agent delivery of a bioactive agent and moreparticularly to methodology and systems for individualization andoptimization of bio-synchronous bioactive agent delivery of a bioactiveagent.

2. Relevant Background

In the field of drug delivery, it is recognized that supplying the drugin a correct temporal pattern is an important attribute of any drugdelivery methodology. Controlled release drug delivery systems areintended to improve response to a drug and/or lessen side effects of adrug. The term “controlled release” refers generally to deliverymechanisms that make an active ingredient available to the biologicalsystem of a host in a manner that supplies the drug according to adesired temporal pattern. Controlled release drug delivery may beimplemented using instantaneous release systems, delayed releasesystems, and sustained release systems. In most cases, controlledrelease systems are designed to maintain a sustained plasma level of anactive ingredient in a drug within a human or animal host over a periodof time.

Instantaneous release refers to systems that make the active ingredientavailable immediately after administration to the bio-system of thehost. Instantaneous release systems include continuous or pulsedintravenous infusion or injections. Such systems provide a great deal ofcontrol because administration can be both instantaneously started andstopped and the delivery rate can be controlled with great precision.However, the administration is undesirably invasive as they involveadministration via a puncture needle or catheter. ‘Delayed release’refers to systems in which the active ingredient made available to thehost at some time after administration. Such systems include oral aswell as injectable drugs in which the active ingredient is coated orencapsulated with a substance that dissolves at a known rate so as torelease the active ingredient after the delay. Unfortunately, it isoften difficult to control the degradation of the coating or encapsulateafter administration and the actual performance will vary from patientto patient. Sustained release generally refers to release of activeingredient such that the level of active ingredient available to thehost is maintained at some level over a period of time. Like delayedrelease systems, sustained release systems are difficult to control andexhibit variability from patient to patient. Due to the adsorptionthrough the gastrointestinal tract, drug concentrations rise quickly inthe body when taking a pill, but the decrease is dependent on excretionand metabolism, which cannot be effectively controlled. In addition, theadsorption through the gastrointestinal tract in many cases leads toconsiderable side effects (such as ulcers), and can severely damage theliver.

Transdermal drug delivery has developed primarily for sustained releaseof drugs in situations where oral sustained release systems areinadequate. In some cases, drugs cannot be effectively administeredorally because the active ingredients are destroyed or altered by thegastrointestinal system. In other cases the drug may be physically orchemically incompatible with the coatings and/or chelating agents usedto implement sustained release. In other cases a transdermal deliverysystem may provide sustained release over a period of days or weekswhereas orally administered drugs may offer sustained performance overonly a few hours. A wide variety of active substances can be deliveredthrough transdermal systems so long as the active substance can beprovided in a form that can cross the skin barrier.

In most cases transdermal delivery systems are passive, taking the formof a patch that is adhesively attached to the host. The patch includes aquantity of the active substance, along with a suitable carrier if needbe, absorbed in a sponge or similar system. Once applied, the activeingredient diffuses into the host through the skin at a rate determinedby the concentration of the active substance and the diffusivity of theactive substance. However, a variety of physical and chemical processesat the skin/patch boundary affect the delivery rate and may eventuallyinhibit drug delivery altogether. Active transdermal delivery systemshave been developed to help regulate the delivery rate by providingmechanisms to improve drug delivery over time by “pumping” the activeingredient. One such system is described in U.S. Pat. No. 5,370,635entitled “DEVICE FOR DELIVERING A MEDICAMENT” which describes a systemfor delivering a medicament and dispensing it to an organism for arelatively long period of time, for example at least a few days. Thedevice can be adapted for positioning on the surface of the skin of ahuman or possibly an animal body in order to apply a medicament theretofrom the outer side thereof.

Conventional transdermal systems circumvent the disadvantages of theadsorption through the gastrointestinal tract, but they do not optimizeor tailor the dosing regiment to offset peak symptoms. In addition theconstant transdermal delivery of a drug can lead to severe side effects,including debilitating sleep disorders and ever increasing tolerance.

Timed delivery is most often used to maintain a sustained level of adrug in the body. A significant focus of current research in drugdelivery has been to determine the influence of a patient's circadian orother biological rhythms on drug efficacy and efficiency. This researchdemonstrates that certain disease symptoms follow a daily pattern, withpeak symptoms at certain times of the day. It has been widelyacknowledged that hormones, neurotransmitters and other intra-bodycompounds are released in different amounts at different times of theday pursuant to daily patterns. The Wall Street Journal reported on May27, 2003 that “Doctors are increasingly looking at the clock when itcomes to prescribing medicine, instructing patients not only to whatdrug to use but also precisely when to take it. This new approach stemsfrom a growing body of research that demonstrates that certain diseasestend to get worse at certain times of the day. By synchronizingmedications with a patient's body clock, many physicians believe thatthe drugs will work more effectively and with fewer side effects. Insome cases, the improvements have been so pronounced that doctors havebeen able to reduce dosages.” Similarly, American Pharmacy reports,“Circadian physiologic processes alter drug absorption, distribution,metabolism, and excretion. As a result, drug doses need to be adjustedto meet the differing needs of target organs or tissues at various timesof the day.”

Recently, an orally administered drug for arthritis treatment hassuggested a chrono-therapeutic approach using a delay release systemwhere the delay is scheduled to release the active ingredient at thebeginning of an interleukin 6 cascade that is believed to cause earlymorning stiffness in rheumatoid arthritis patients. By attempting tosynchronize the drug delivery with a biological cycle it is believedthat low doses may be used to achieve desired results. However, thissystem does not overcome the limitations of delayed release systemsdescribed above. Although it may be possible to meet the requirements ofchrono-pharmacology with pills, such an effort requires an enormousamount of discipline by the patient to comply with the treatmentregiment. For example, to achieve optimal results, many patients mayneed to wake up during the night to take their medication.

Currently, patient compliance (taking the proper dosages at theprescribed times) is a critical problem facing caregivers andpharmaceutical firms alike. Studies show that only about half ofpatients take medications at the times and in the dosages directed bytheir physician. It is reported that each year, 125,000 deaths and up to20% of all hospital and nursing home admissions result from patientnon-compliance. And it is estimated that non-compliance results inadditional healthcare costs in excess of $100 billion per year in UnitedStates. These figures are even more pronounced for the elderly. Hence, aneed exists for systems and methods that increase patient compliance aswell as administration of a variety of drugs.

One successful Chrono-Therapeutic approach involves synchronizing theadministration of compounds with the human body's natural circadianrhythms and addiction rhythms to counteract symptoms when they arelikely to be at their worst by using an automated transdermal or otherdrug administration system. As described in U.S. Pat. No. 7,780,981,“Biosynchronous Transdermal Drug Delivery”, a device delivers varyingdosages at varying times, pursuant to a pre-programmed dosage profile.This ensures that peak drug concentrations are present in thebloodstream to offset peak disease and/or addiction symptoms arisingfrom variances and fluctuation in the body's natural circadian rhythms.

While the '981 patent is a tremendous advance in transdermal drugapplication, the determination of an individuals circadian and biologicrhythm can be a challenge. Moreover, for the efficacy of the treatmentprotocol to be maximized, the delivery of the pharmacology must bealigned with the needs of each individual. As there is a finite anddeterminable amount of time from the point of delivery of the drug toits effect, the chosen drug would ideally be delivered immediately priorto the onset of a symptom such as an addictive craving. Accordinglyidentifying, predicting the onset of a symptom, a craving, and itsintensity, is a necessary component to effective addiction cessationtreatment. Furthermore, once identified these physiologically andpsychological demands must be converted to an individualized dosageprofile to optimize efficacy.

It is also widely recognized that the physiological characteristics ofan illness also have a psychological effect on a patient and, likewise,that a patient's psychological condition can directly impact one'sphysiological health. Yet treatment protocols often fail to take intoaccount these two closely interrelated aspects of healthcare. It iswidely accepted that emotional support offered by help lines or groupdiscussions can assist an individual to overcome the conditionsassociated with a physical ailment. Nine-step programs and the like haveresounding success regarding addictive related conditions yet few suchprograms are integrated into pharmacological treatment protocols. Whatis needed therefore is a comprehensive treatment regime that combines atemporally appropriate and biometrically synchronized pharmacologicaltreatment, the ability to monitor a patient's compliance with thetreatment plan, and suitable emotional support. These and otherchallenges of the prior art are addressed by one or more embodiments ofthe present invention.

Additional advantages and novel features of this invention shall be setforth in part in the description that follows, and in part will becomeapparent to those skilled in the art upon examination of the followingspecification or may be learned by the practice of the invention. Theadvantages of the invention may be realized and attained by means of theinstrumentalities, combinations, compositions, and methods particularlypointed out in the appended claims.

SUMMARY OF THE INVENTION

A system and associated methodology for an optimized bio-synchronousdrug delivery begins with establishing a bio-synchronous treatmentprotocol that incorporates individual temporal and innate biologicalcharacteristics into a pharmacological treatment plan. Thebio-synchronous treatment protocol is thereafter initiated by the user,or associated healthcare provider using, in one embodiment a bioactiveagent delivery device. The bio-synchronous drug delivery system andmethodology further includes continually gathering patient data duringthe bio-synchronous treatment protocol including physical,psychological, temporal and environmental characteristics. Oncecollected this data is analyzed so to not only determine an initialtreatment protocol but to also determining whether modification to theongoing bio-synchronous treatment protocol is required. And, responsiveto determining modification to the bio-synchronous treatment protocol isrequired the system modifies the bio-synchronous treatment protocol anduse of the bio-synchronous bioactive agent delivery device and theniteratively assesses its optimization to see if additional modificationsare warranted.

Other features of the present invention include temporal administrationof pharmacological elements based on individual patient temporalpatterns and/or on patient innately rhythmic biological processes. Thebio-synchronous treatment protocol of the present invention alsoincludes temporal psychological support that can be linked to patient'stemporal patterns or linked to patient's innately rhythmic biologicalprocesses. Moreover, temporal psychological support can be proactivelybased on the bio-synchronous treatment protocol or reactive based on apatient's current emotional state. This temporal psychological supportcan include an electronic message, direct interaction with psychologicalsupport personnel and the like.

The optimized bio-synchronous bioactive agent deliver device of thepresent invention further includes the ability to monitor compliancewith the bio-synchronous treatment protocol and collect patientphysiological data and patient psychological data. Such data caninclude, for example, a patient reported emotion such a craving, intenseanxiety, or pain.

Using this information the present invention can modify the currenttreatment protocol, including, in one embodiment, modifying theadministration of the protocol remotely.

Another embodiment of the present invention includes method foroptimized bio-synchronous drug delivery of a bio-synchronous treatmentprotocol that includes the steps of collecting patient data during useof a bio-synchronous bioactive agent delivery device according to thebio-synchronous treatment protocol, analyzing the collected data duringongoing use of the bio-synchronous bioactive agent delivery device, and,if necessary, modifying the bio-synchronous treatment protocol. All ofwhich is done during use of the bio-synchronous bioactive agent deliverydevice.

In addition to the methodology described above the present invention, inone embodiment, further includes a system for optimized bio-synchronousdrug delivery. Such a system can include, a bio-synchronous treatmentprotocol and an associated bio-synchronous bioactive agent deliverydevice configured to administer pharmacological elements of thebio-synchronous treatment protocol. The system also includes patientdata gathered during administration of the bio-synchronous treatmentprotocol that is analyzed by an analysis module and which is furtheroperable to optimize the bio-synchronous treatment protocol based onthat analysis.

Such a system can also include a communication module operable tocommunicate (wirelessly in some embodiments) the modifiedbio-synchronous treatment protocol to the delivery device. Such abio-synchronous treatment protocol can include pharmacological elementstemporally administered based on individual patient temporal patternsand/or individual patient innately rhythmic biological processes.

The system also can include, in other embodiments, temporalpsychological support engine or module. This support module and itsassociated processes can be linked to patient temporal patterns and/orto patient innately rhythmic biological processes. The psychologicalsupport module can further be proactively initiated on thebio-synchronous treatment protocol as well as reactive to addressimmediate patent needs. In one version of the present invention temporalpsychological support includes electronic messages or direct interactionwith psychological support personnel.

Another feature of the present invention the ability to gather patientcompliance, physiological and psychological data and when warranted,modify the current and ongoing treatment protocol. The system caninclude applications resident on a smart phone or similar device thatcan record and report patient physiological/physiological data such as acraving, anxiety or experience of intense pain. Using this, and other,information, the system of the present invention can not only offeremotional support, but also modify the ongoing treatment protocol toprovide an optimized bio-synchronous bioactive agent delivery system.

The features and advantages described in this disclosure and in thefollowing detailed description are not all-inclusive. Many additionalfeatures and advantages will be apparent to one of ordinary skill in therelevant art in view of the drawings, specification, and claims hereof.Moreover, it should be noted that the language used in the specificationhas been principally selected for readability and instructional purposesand may not have been selected to delineate or circumscribe theinventive subject matter; reference to the claims is necessary todetermine such inventive subject matter.

BRIEF DESCRIPTION OF THE DRAWINGS

The aforementioned and other features and objects of the presentinvention and the manner of attaining them will become more apparent,and the invention itself will be best understood, by reference to thefollowing description of one or more embodiments taken in conjunctionwith the accompanying drawings, wherein:

FIG. 1 is a high level system diagram of an environment for the use ofan optimized bio-synchronous bioactive agent delivery system accordingto one embodiment of the present invention;

FIG. 2 depicts a network diagram suitable for the implementation of anoptimized bio-synchronous bioactive agent delivery system according toone embodiment of the present invention;

FIGS. 3A and 3B, correctively FIG. 3, are high level flowcharts of amethod for transdermal drug delivery optimization and emotional supportaccording to one embodiment of the present invention;

FIG. 4 is a high level flowchart of a method for determination of abioactive agent delivery protocol and facilitating patient drug deliverycompliance and cessation advocacy according to one embodiment of thepresent invention; and

FIG. 5 is a high level flowchart of a method of optimizedbio-synchronous bioactive agent delivery according to one embodiment ofthe present invention.

The Figures depict embodiments of the present invention for purposes ofillustration only. Like numbers refer to like elements throughout. Inthe figures, the sizes of certain lines, layers, components, elements orfeatures may be exaggerated for clarity. One skilled in the art willreadily recognize from the following discussion that alternativeembodiments of the structures and methods illustrated herein may beemployed without departing from the principles of the inventiondescribed herein.

DESCRIPTION OF THE INVENTION

Research demonstrates that certain disease symptoms follow a dailypattern, with peak symptoms at certain times of the day. It has beenwidely acknowledged that hormones, neurotransmitters and otherintra-body compounds are released in different amounts at differenttimes of the day pursuant to daily patterns. These temporal symptoms arevividly apparent in addiction ailments. For example, according tostudies performed, immediately upon waking, smokers typically have peaknicotine cravings. These peak cravings return after each meal, due tothe interplay of serotonin release as a trained response to theculmination of a meal. Precisely timing the administration of addictioncessation drugs so that they reach peak levels when symptoms are likelyto be at their worst, greatly improves the efficacy of these drugs.

Critical to the administration of these drugs is the accurate andindividualistic temporal determination regular and peak cravingepisodes. The present invention provides a means by which symptoms,cravings and desires, are individualistically identified to form adosage profile. In addition to identifying when a symptom occurs, suchas a craving, and its intensity, the present invention gathers othervital information so as to modify (wirelessly in some embodiments) theadministration drug administration profile to be maximally effective.According to one embodiment of the present invention a digitalapplication presents a user interface that enables a user to quickly andeffectively input time sensitive data related to a particular symptom.Using a device such as smartphone, PDA or the like, a user can, uponexperiencing a symptom, memorialize and convey the experience. Theapplication in one embodiment can assist the user in identifying theintensity of the symptom as well as logging when the symptom occurred.Using that data, along with additional profile data of the user, a drugdelivery or treatment protocol can be determined and thereafterdelivered to a drug delivery device for execution.

Cessation and treatment of addictive behavior is of but one applicationof the advances associated as in the present invention. While thedescription that follows often describes the invention with reference tothe cessation of an addictive behavior, smoking for example, on ofreasonable skill in the relevant art will recognize that the features ofthe present invention are equally applicable access a wide range ofdisease treatment protocols. For example, the same advances describedherein can be used to improve and optimize treatment for cardiacdisease, diabetes, psychotic episodes, pain management, and the like.The present description is provided by way of example and the focus onsmoking cessation should not be interpreted as limiting the invention.

Embodiments of the present invention further enhance the efficacy of thedrug treatment protocols by providing real time psychological andemotional support. Addiction and smoking cessation support groups forexample remain available to the users of the present invention howeverthese types of support mechanisms are enhanced with the utilization ofsocial media and follow up patient interface of the present invention.Websites and social media services such as Facebook® and Twitter® canprovide access to smoking cessation tools when properly accessed andchat rooms, hot-lines, tips and so on can provide the user withemotional support in addition to the pharmacological assistance toovercome the urge to smoke. The present invention, upon gaininginformation leading to the determination of a immediate symptom, acraving or aberrant desire to smoke in the case of addiction tonicotine, can not only modify the drug treatment protocols but providethe user with a supportive tip, text, voice mail, vibrating tone, or anyother for of communicative message, to support their emotional need torepel the craving and follow the treatment protocol.

Embodiments of the present invention are hereafter described in detailwith reference to the accompanying Figures. Although the invention hasbeen described and illustrated with a certain degree of particularity,it is understood that the present disclosure has been made only by wayof example and that those skilled in the art can resort to numerouschanges in the combination and arrangement of parts without departingfrom the spirit and scope of the invention.

Reference to the accompanying drawings is provided to assist in acomprehensive understanding of exemplary embodiments of the presentinvention as defined by the claims and their equivalents. Thespecification includes various specific details to assist in thatunderstanding but these are to be regarded as merely exemplary.Accordingly, those of ordinary skill in the art will recognize thatvarious changes and modifications of the embodiments described hereincan be made without departing from the scope and spirit of theinvention. Also, descriptions of well-known functions and constructionsare omitted for clarity and conciseness.

The terms and words used in the following description and claims are notlimited to the bibliographical meanings, but are merely used by theinventor(s) to enable a clear and consistent understanding of theinvention. Accordingly, it should be apparent to those skilled in theart that the following description of exemplary embodiments of thepresent invention are provided for illustration purpose only and not forthe purpose of limiting the invention as defined by the appended claimsand their equivalents.

Unless otherwise defined, all terms (including technical and scientificterms) used herein have the same meaning as commonly understood by oneof ordinary skill in the art to which this invention belongs. It will befurther understood that terms, such as those defined in commonly useddictionaries, should be interpreted as having a meaning that isconsistent with their meaning in the context of the specification andrelevant art and should not be interpreted in an idealized or overlyformal sense unless expressly so defined herein. Well-known functions orconstructions may not be described in detail for brevity and/or clarity.

Like numbers refer to like elements throughout. In the figures, thesizes of certain lines, layers, components, elements or features may beexaggerated for clarity.

The terminology used herein is for the purpose of describing particularembodiments only and is not intended to be limiting of the invention. Itis to be understood that the singular forms “a,” “an,” and “the” includeplural referents unless the context clearly dictates otherwise. Thus,for example, reference to “a component surface” includes reference toone or more of such surfaces.

By the term “substantially” it is meant that the recited characteristic,parameter, or value need not be achieved exactly, but that deviations orvariations, including for example, tolerances, measurement error,measurement accuracy limitations and other factors known to those ofskill in the art, may occur in amounts that do not preclude the effectthe characteristic was intended to provide.

It will be understood that when an element is referred to as being “on”,“attached” to, “connected” to, “coupled” with, “contacting”, etc.,another element, it can be directly on, attached to, connected to,coupled with or contacting the other element or intervening elements mayalso be present. In contrast, when an element is referred to as being,for example, “directly on”, “directly attached” to, “directly connected”to, “directly coupled” with or “directly contacting” another element,there are no intervening elements present. It will also be appreciatedby those of skill in the art that references to a structure or featurethat is disposed “adjacent” another feature may have portions thatoverlap or underlie the adjacent feature.

Spatially relative terms, such as “under”, “below”, “lower”, “over”,“upper” and the like, may be used herein for ease of description todescribe one element or feature's relationship to another element(s) orfeature(s) as illustrated in the figures. It will be understood that thespatially relative terms are intended to encompass differentorientations of a device in use or operation in addition to theorientation depicted in the figures. For example, if a device in thefigures is inverted, elements described as “under” or “beneath” otherelements or features would then be oriented “over” the other elements orfeatures. Thus, the exemplary term “under” can encompass both anorientation of “over” and “under”. The device may be otherwise oriented(rotated 90 degrees or at other orientations) and the spatially relativedescriptors used herein interpreted accordingly. Similarly, the terms“upwardly”, “downwardly”, “vertical”, “horizontal” and the like are usedherein for the purpose of explanation only unless specifically indicatedotherwise.

Included in the description are flowcharts depicting examples of themethodology that may be used to determine individualized an optimizeddosage profiles for bioactive agent delivery. In the followingdescription, it will be understood that each block of the flowchartillustrations, and combinations of blocks in the flowchartillustrations, can be implemented by computer program instructions.These computer program instructions may be loaded onto a computer orother programmable apparatus to produce a machine such that theinstructions that executes on the computer or other programmableapparatus create means for implementing the functions specified in theflowchart block or blocks. These computer program instructions may alsobe stored in a computer-readable memory that can direct a computer orother programmable apparatus to function in a particular manner suchthat the instructions stored in the computer-readable memory produce anarticle of manufacture including instruction means that implement thefunction specified in the flowchart block or blocks. The computerprogram instructions may also be loaded onto a computer or otherprogrammable apparatus to cause a series of operational steps to beperformed in the computer or on the other programmable apparatus toproduce a computer implemented process such that the instructions thatexecute on the computer or other programmable apparatus provide stepsfor implementing the functions specified in the flowchart block orblocks.

Accordingly, blocks of the flowchart illustrations support combinationsof means for performing the specified functions and combinations ofsteps for performing the specified functions. It will also be understoodthat each block of the flowchart illustrations, and combinations ofblocks in the flowchart illustrations, can be implemented by specialpurpose hardware-based computer systems that perform the specifiedfunctions or steps, or combinations of special purpose hardware andcomputer instructions.

Some portions of this specification are presented in terms of algorithmsor symbolic representations of operations. These operations may includedata stored as bits or binary digital signals within a machine memory(e.g., a computer memory). These algorithms or symbolic representationsare examples of techniques used by those of ordinary skill in the dataprocessing arts to convey the substance of their work to others skilledin the art. As used herein, an “algorithm” is a self-consistent sequenceof operations or similar processing leading to a desired result. In thiscontext, algorithms and operations involve the manipulation ofinformation elements. Typically, but not necessarily, such elements maytake the form of electrical, magnetic, or optical signals capable ofbeing stored, accessed, transferred, combined, compared, or otherwisemanipulated by a machine. It is convenient at times, principally forreasons of common usage, to refer to such signals using words such as“data,” “content,” “bits,” “values,” “elements,” “symbols,”“characters,” “terms,” “numbers,” “numerals,” “words”, or the like.These specific words, however, are merely convenient labels and are tobe associated with appropriate information elements.

Unless specifically stated otherwise, discussions herein using wordssuch as “processing,” “computing,” “calculating,” “determining,”“presenting,” “displaying,” or the like may refer to actions orprocesses of a machine (e.g., a computer) that manipulates or transformsdata represented as physical (e.g., electronic, magnetic, or optical)quantities within one or more memories (e.g., volatile memory,non-volatile memory, or a combination thereof), registers, or othermachine components that receive, store, transmit, or displayinformation.

As used herein any reference to “one embodiment” or “an embodiment”means that a particular element, feature, structure, or characteristicdescribed in connection with the embodiment is included in, but notlimited to, at least one embodiment. The appearances of the phrase “inone embodiment” in various places in the specification are notnecessarily all referring to the same embodiment.

As used herein, the terms “comprises,” “comprising,” “includes,”“including,” “has,” “having” or any other variation thereof, areintended to cover a non-exclusive inclusion. For example, a process,method, article, or apparatus that comprises a list of elements is notnecessarily limited to only those elements but may include otherelements not expressly listed or inherent to such process, method,article, or apparatus. Further, unless expressly stated to the contrary,“or” refers to an inclusive or and not to an exclusive or. For example,a condition A or B is satisfied by any one of the following: A is true(or present) and B is false (or not present), A is false (or notpresent) and B is true (or present), and both A and B are true (orpresent).

Determination of patient treatment protocol compliance has long been achallenge. An optimal drug dosage protocol often relies on precisecontrol of several environmental factors such when (and if) a patientadministers the proper dosage. The apparent low efficacy of a particulardrug may be attributed to many factors but often it can be attributed topoor adherence by the patient of administration protocols. For example aparticular drug may be optimally administered 4 times daily withapproximate 6-hour intervals between administrations. Yet it is notuncommon to find that a patient, having complained that the drug hasbeen ineffective, has missed one or two administrations of the drug orthat rather than a 6-hour interval between dosages, the intervals varyfrom 4 to 8 hours.

One means by which to increase patient compliance is through a systemthat automatically and temporally delivers prescribed medicine withminimal patient interaction. Such innovation is present in abio-synchronous bioactive agent delivery device of the presentinvention.

One embodiment useful for bioactive agent delivery and according to thepresent invention includes an absorbent material pretreated or combinedwith a bioactive agent. The term “absorbent material” refers herein to amaterial having the capacity or tendency to absorb another substance.The term “bioactive agent” refers herein to a substance that has aneffect on a living organism.

Bioactive agents (or combinations thereof) suitable for transdermal andsimilar drug delivery include but are not limited to hormonalcontraceptives, pain relievers, antidepressants, stimulants fortreating, for example, ADHD, biopharmaceuticals, active agents useful intreating chronic conditions, opioids, alprazolam, apomorphine,azelastine, alprostadil, buprenorphine, bupropion, clonidine,dexamethasone, dextroamphetamine, diclofenac, dihydrotestosterone,enalpril, estradiol, androgen/estradiol, estrodiol/progestin,testosterone/estradiol, ethinyl estradiol, fentanyl, flurbiprofen,glucagon-like peptide 1, glucagon-like peptide 2, granisetron, insulin,lidocaine, memantine, methylphenidate, methamphetamine, nitroglycerine,nicotine, norethisterone acetate (NETA), norelgestromine, oxybutynin,parathyroid hormone, pergolide, phenteramine, pramipexole, ramipril,ropinirole, rotigotine, scopolamine, selegiline, tecrine, testosterone,timolol, tolterodine, tulobuterol, and vaccines.

Conditions effectively treated with bioactive agents deliveredtransdermally include but are not limited to anxiety, allergies,depression, hypertension, nausea, diabetes, neuralogic pain, Alzheimer'sdisease, obesity, smoking cessation, urinary incontinence, Parkinson'sdisease, motion sickness, male hypogonadism and female sexualdysfunction.

In this embodiment of a bioactive agent delivery device a pretreatedabsorbent material is associated with a reservoir that includes asolution and a membrane permeable to the bioactive agent. The absorbentmaterial pretreated with bioactive agent is interposed between thereservoir and the membrane. In response to a control signal generated bythe device through an internal timing mechanism or remotely triggered,the solution is dispensed from the reservoir and is received by theabsorbent material pretreated with bioactive agent. The solutionfacilitates transfer of the bioactive agent from the absorbent materialto the membrane. The membrane is in contact with the epidermis of a host(a human or an animal). As the membrane is permeable to the bioactiveagent, this compound diffuses through the membrane from the absorbentmaterial and into the epidermis of the host. In this way, bioactiveagent is transdermally administered to the host of the drug deliverysystem.

In one embodiment of the present innovation, a solution is activelydispensed from the reservoir by a delivery mechanism that comprises amode of force. The mode of force can be pressure which, for example,includes but is not limited to compressed foam, one or more gasgenerating cells and the like. By applying pressure to the solution inthe reservoir, the solution is dispensed from the reservoir through avalve operable to control the flow of the solution from the reservoir tothe absorbent material pretreated with bioactive agent. In accordancewith another embodiment of the present innovation, a pump functions asthe delivery mechanism operable to dispense the solution from thereservoir to the absorbent material pretreated with bioactive agent.

As mentioned, a timing mechanism is communicatively coupled to thedelivery mechanism and is operable to generate the control signal todispense the solution from the reservoir to the absorbent materialpretreated with bioactive agent. In one embodiment of the presentinnovation, the timing mechanism communicatively coupled to the deliverymechanism is configured to generate the control signal according to aprogrammed administration schedule. In other embodiments the controlsignal can be remotely delivered to the device to signal application ofthe solution to the permeable membrane. As an example, the drug deliverydevice can be coupled to a human and programmed to administer a compoundduring sleep. By using this system, the patient is appropriately dosedwithout having to be inconvenienced by waking up and personallyadministering the bioactive agent.

One feature of the present invention collects patient compliance dataregarding use of a bioactive agent delivery system and to uses thatcompliance data as a basis for near real-time modifications of treatmentprotocols and, when necessary, to initiate non-pharmaceutical behavioralsupport. The bioactive agent deliver device of the present inventionprovides a means by which to deliver a pharmacological agent to thepatient via transdermal interaction.

These delivery mechanisms can include but are not limited toiontophoresis, micro-needles, sonoporation, transdermal diffusion,dermal abrasion, control heat activated transdermal delivery orsubcutaneous drug delivery. As one of reasonable skill in the relevantart will appreciate, iontophoresis is a physical process in which ionsflow diffusively in a medium driven by an electric field. Iontophoresisis to be distinguished from the carriage of uncharged molecules bydiffusive fluxes of other molecules, especially of solvent molecules,for example by electro-osmosis, that is to say by flux of unchargedsolvent molecules carried as a cross-effect of iontophoresis.Iontophoresis is thus active transport of matter due to an electricfield.

Another means by which to transport medicine transdermally employsmicro-needles. Micro-needles use bio-compatible, medical grade polymericmicrostructures to overcome the dermal barrier properties of the stratumcorneum so as to deliver a wide range of biopharmaceutical therapeutics.Micro-needles can be employed as a patch or device containing a varietyof microstructures that penetrate and deliver the medication.

Sonoporation, or cellular sonication, is another means by which totransdermally deliver medication. Sonoporation is the use of sound(typically ultrasonic frequencies) for modifying the permeability of thecell plasma membrane so as to allow therapeutic treatment. Sonoporationemploys the acoustic cavitation of micro-bubbles to enhance delivery oflarger molecules to a cell. Controlled heat activated transdermaldelivery, as another deliver means, uses heat to enhancemicrocirculation and local perfusion and/or blood vessel permeability soas to facilitate drug transfer to the systemic circulatory system.Similarly, a subcutaneous injection can administer the drug into thesubcutis, the layer of skin directly below the dermis and epidermis,collectively referred to as the cutis. Subcutaneous injections arehighly effective in administering vaccines and medications such asinsulin, morphine, diacetylmorphine and goserelin. Each of thesetechnologies, and the like, provide a means by which to administer apharmacological agent to a patient via the dermal layer and can beadapted for use with the optimized bisynchronous bioactive agentdelivery system of the present invention.

A bioactive agent dosage (treatment) protocol for use with one or moreembodiments of the present invention is developed based on a variety ofparameters. For example, a physician or addiction cessation specialistmay collect data with respect to physiological and psychological factorsto help determine which drug should be used an its initial dosageamounts. These factors may include the patient's gender, age, length ofadditive behavior, the type of addiction or ailment being treated, andconditional factors such as the environment in which the patient worksor lives, etc. As previously discussed imputing into the drug dosageprotocols (also referred to herein as the bio-synchronous and/ortemporal treatment protocol) individual biorhythms and temporal cyclesenhances the efficacy of the bioactive agent delivery system of thepresent invention. Indeed the treatment protocol of the presentinvention includes bio-synchronous and temporal administration ofpharmacological elements based on patient innately rhythmic biologicalprocesses and/or individual patient temporal patterns. These treatmentprotocols can take into account individual biorhythms, pharmacologicaland ailment temporal factors as well as individualized temporalcycles/schedules. Recall that biorhythms are rhythmic biological cyclesthat affect one's ability in various domains, such as mental, physicaland emotional activity. According to one theory these cycles begin atbirth and oscillate in a steady (sine wave) fashion throughout life.Sinusoidal behavior would be expected from chemical and hormonalsecretion functions with their biofeedback activity with respect tochemical concentration. While still controversial there is evidence thatindividuals do experience cyclic tendencies. Similarly certain ailmentsare more prevalent during aspects of an individual's daily (or othertime period) cycle. For example, heart ischemia resulting in angina canbe caused by spasm of the coronary arteries. This is a rare conditioncalled vasospastic angina (also known as Prinzmetal's angina) and is notassociated with exertion. It is also well documented that the symptomsof ischemic heart disease are more common in the morning hours than atany other time of day. Yet an individuals “morning hours” vary based onseveral factors. One individual may regularly wake at 6:00 AM and retireat 10:00 PM. Another may find 9:00 AM the more likely time to arise andretire at 2:00 AM. And yet another may work evenings and find their“morning hours” begin at 1:00 PM and they retire at 5:00 AM. While thereis evidence that humans are affected by the diurnal and nocturnalcycles, symptoms associated with medical conditions and ailments can beaffected by an individual schedules. The treatment protocols of thepresent invention account for numerous temporal and cyclic factorsaffecting a patient's symptoms. The treatment protocol of the presentinvention for an individual suffering from a cold or from influenza, forexample, may find that a pharmacological treatment is applied based onfactors such as when that individual normal goes to bed, arises and goesto work, their age, their gender, certainly the type disease/virus if itcan be identified, their mental state, and any other factor that can beused to make the treatment be as individually effective as possible.Thus the term bio-synchronous is used, herein, broadly to be inclusiveof a plethora of temporal and biological factors.

As with any patient administered medication, compliance with a treatmentprotocol is critically important in the determination of the drugsefficacy and whether the treatment protocol should be modified.According to one embodiment of the present invention, the bioactiveagent delivery device maintains a precise record of dosages and deliverytimes of the prescribed medication. This data can therefor be wirelesslyreported to a health professional or medical specialist for analysis. Inother embodiments, the data can be used to initiate automated responsesand adjustments to the treatment protocol based on established treatmentalgorithms. Using collected compliance data a medical specialist canassess the effect of the drug on the patient's symptoms with confidencethat the prescribed treatment protocol has been followed. Similarly, ifa patient reports that the desired or anticipated effect of thetreatment protocol has not occurred, the medical specialist can assesswhether the drug as been administered according to the predefinedprotocol before altering the treatment protocol. If the compliance datamatches the predefined treatment protocol the specialist can, ifwarranted, modify the dosages or other protocol factors. If however thecompliance data provides evidenced that the treatment regime was notfollowed, the specialist can accordingly stress with the patient theneed to follow the treatment procedures as closely as possible orsuggest other treatment processes.

FIG. 1 provides a high level depiction of a system for optimizedbio-synchronous bioactive agent delivery. As shown, a user 110 employs abio-synchronous bioactive agent deliver system 120 to implement apredetermined drug dosing protocols. The bio-synchronous bioactive agentdelivery system 120 is initiated based on input from the user 110 asdirected by a medical specialist. For example the user (patient) mayinput data into the device information such as normal waking hours, workregimes, meal times, sleep schedule, etc. Based on that information thebio-synchronous bioactive agent delivery system 120 can usingalgorithmic dosing processes, administer a select drug within apredetermined temporal dosing schedule. Algorithmic dosing is based ondata collected from the patient. In addition, a compliance unit 130,coupled to the bio-synchronous bioactive agent delivery system 120, cancollect and report data with respect to administration of the prescribeddosage. Upon the user setting up and initiating the bio-synchronousbioactive agent delivery system 120 the compliance unit 130 isactivated. Along with directing the bio-synchronous bioactive agentdelivery system 120 to administer a dose of medicine to the patient at abisynchronous time, the compliance unit records and, in otherembodiments, reports compliant events. Event details such as the time ofthe administration, the amount of the dose, the point at which dosingwas ceased, and other biometric factors can be collected, stored, andreported. Moreover the system can determine, in one embodiment, whetherthe user removed the device, a treatment was missed, or if treatment wasinterrupted. Other embodiments can further collect physiological datasuch as pulse, temperature and blood pressure to assist in assessing theimpact of treatment protocol.

To aid in reporting of data, the compliance unit 130 can furtherinclude, in one embodiment, a wireless transceiver 150 and a processor160 for local processing of the treatment protocols and for conveyingcompliance information to a remote administrator. In one version of thepresent invention the medical specialist administrating the treatmentcan be informed of noncompliance with the treatment protocol so as tomake contact with the patient via text or phone regarding non-complianceof the treatment protocol. For example upon the system detecting that itcannot administer a scheduled dose of medicine the non-compliance unit130 can report the transgression to an administrator who can contact thepatient and, if necessary, offer behavioral support to re-initiate thetreatment protocols. In other embodiments the collected data can bedownloaded upon a patient's regular medical visit to assess the overalleffect of the treatment program. In another embodiment of the presentinvention, non-compliance data can be used as an input to an algorithmicprocess by which automated emotional support is initiated. For example,a report of non-compliance can trigger an automated message to encouragethe patient to re-initiate treatment or contact their healthcareprovider.

Another innovation, according to the present invention, is the abilityto collect individual psychological and physiological data with respectto the effect of a particular disease and use such information toindividually optimize a drug treatment protocol. For example, in thecase of nicotine addiction, a smoker's craving for a cigarette or asimilar nicotine delivery device may peak at certain periods of timeduring the day. These peaks may vary in intensity and timing from oneperson to the next. Research has shown that many smokers have an intensecraving for cigarettes early in the morning, at lunchtime, in theevening after dinner, and before retiring for sleep, but the exacttiming of these cravings differs in each individual. One embodiment ofthe present invention enables the user, in this case a smoker, to easilydocument and report when the craving for a cigarette occurs and rate theintensity of the craving.

According to one embodiment of the present invention an applicator, orsimilar user interface, on a smart phone, tablet or computer can quicklylog details with respect to the experienced symptom. Details such as thetime of the recordation of the event can automatically be requested butthe application, based on the treatment protocol, can present thepatient with a short, but effective inquiry to gain important detailswith respect to the symptom. In the case of a craving for a cigarettethe application can ask when the craving occurred, what was theintensity, did the patient smoke a cigarette, was the patient understress, when was the last med, and the like. This information can thenbe used to optimize the treatment protocol.

Using a temporal log of such inputs, algorithms can in one embodiment,determine the best (optimal) dosage application of nicotine or othercessation type of drugs to facilitate an optimized smoking cessationprotocol to be administered by the bisynchronous drug delivery system ofthe present invention. These protocols can be individualized not onlyfor the particular pharmacology being used but also for thephysiological and psychological profile of the user. Moreover, thisinformation can be correlated with user compliance information todetermine whether the cravings and established treatment protocols ofthe bio-synchronous bioactive agent delivery system 120 are properlyoptimized.

Dosage and compliance administration data can further includeinformation about whether or not, as well as when, a patient has beenadministered a particular dosage of medication. The dosage data isconfirmatory information and can, in one embodiment, only be generatedwhen the bio-synchronous bioactive agent delivery system 120 makescontact with the users skin 110 and administers the medication. Thusthis type of compliance information is different (and more accurate andreliable) than self reported information or data that may be generatedby a proxy. The present system does not rely on patient interaction orrecordation of the event. Once initiated, the application of medicationis recorded, and in one embodiment, reported to a centralized server orsecondary device for analysis.

In addition to dosage administration data, additional data, as describedearlier, may be obtained from the patient using, an application on asmartphone or similar electronic device. Patient data may be obtainedsuch as: physiological parameter data, e.g., as may be obtained using asensing device, including biological and physiological sensors;lifestyle data, such as historical information about the patient (e.g.,the patients activities on a given day, how the patient was feeling,etc.) as well as physiological data such as the patient's feelings ofcravings or anxiety; activities of the patient (e.g., whether or not thepatient expects to exercise, whether or not the patient is feeling well,etc.); and the like.

Compliance and ancillary data gained from the patient and drug deliverydevice is then evaluated to determine whether a change in the treatmentprotocol is warranted and if so, provide a recommendation based on thatdetermination. The dosage administration data can also be assessed toidentify whether, based on the information received from the patient,such as compliance data, physiological parameters and lifestyle data,any modification should be made to the therapeutic regimen and treatmentprotocols in order to optimize the therapeutic regimen for the patientin some way. For example, based on patient inputter and compliance datait may be determined that the treatment protocol needs to be shifted totemporarily so as to initiate medication earlier.

A health care practitioner may evaluate the data, e.g., manually orthrough use of any convenient decision tool that may include a database,algorithm, actionable interface (e.g., in the form of a graphical userinterface (GUI)), outcome measure, etc. The health care professional orsimilar individual may then employ the resultant recommendation based onthis step and if necessary communicate the determination to the patientand/or device directly. In one embodiment of the present inventioncommunication of the change in dosage or temporal protocols can becommunicated verbally while the bioactive agent delivery system can bemodified remotely. Alternatively, the health care practitioner mayinform the patient that no change in therapeutic regimen should be madeand that the patient should continue to follow the therapeutic regimenas previously specified to the patient.

The modulation of the therapeutic regimen, when made, may take a varietyof different formats. For example, the modulation may take the form of achange in a pharmaceutical dosage regimen, e.g., in the amounts ofactive agent taken and/or the different types of active agents taken orthe duration of the treatment. The modulation may also take the form ofa change in the activity of the bioactive agent delivery system. Inaddition, the modification may include lifestyle alterationrecommendations, e.g., instructions to refrain from exercise,instructions to engage in exercise, instructions to modify diet, and thelike. As mentioned, one feature of the present invention is the abilityto wirelessly communicate with the bioactive agent application device soas to control the dosage and temporal delivery of a particularpharmacology. In one embodiment of the present invention thedetermination of the delivery protocol can be calculated and thereafterdelivered to the delivery device wirelessly while in another embodimentthe delivery device receives raw data from the data collection deviceand then formulates the revised delivery protocols locally. Inalternative embodiments the protocols and the delivery mechanisms aredetermined and delivered on a distributive basis.

As mentioned, one or more embodiments of the present invention involvesan application that would reside on a smartphone, laptop, PDA, or thelike in which an individual's personal data is used to form a profile asthe basis for determining dosage amounts and the timing thereof. Forexample information such as the gender of the individual, age, weight,and the like can be gathered in the formation of a profile and then usedin conjunction with the cravings data to determine proper dosages, orthe need of a bolus (a one time administration of medication), and whenthose dosages should be applied. Other disease specific information canalso be gathered such as (for smoking cessation) how many cigarettesdoes the user normally smoke in a day, the type and strength of thesecigarettes, does the user smoke when consuming alcohol, or coffee, andthe like. The application can prompt the user to answer questions ontopics ranging from the current emotional state, the urge to smoke atthat moment in time, if they had smoked during the day or within apreceding period of time, smoking events, and/or other emotional orenvironmental factors that may contribute to their desire to smoke. Alsothe program can establish how motivated or driven the individual is withrespect to smoking cessation. For example, the protocol for a heavysmoker that only wants to decrease the number of cigarettes he or shedesires during the course of a day may differ from a light smoker maywant to cease smoking altogether. Furthermore, another individual maywant to quit smoking within a predetermined period of time, for examplea month, while another smoker may want to gradually decrease the numberof cigarettes they smoke each day over a period of six months to arrivesmoke-free at some particular goal date. Each of these inputs affectsthe dosage and temporal application of the appropriate cessation drugbased on a differing algorithm approach.

FIG. 2 shows a high-level network environment in which a system foroptimized bio-synchronous bioactive agent delivery can be implemented.As shown, the bio-synchronous bioactive agent delivery system of thepresent invention is, in one embodiment, communicatively coupled to anetwork 210 such as the Internet or an Intranet. A personal dataassistant, smartphone, tablet or the like 230 can also collect andconvey user information via the network 210, in addition to thebio-synchronous bioactive agent delivery system 220, to an analysis oradministration server 250. The administrative server 250 can furtherpossess storage devices 255 to memorialize and retain the data forfurther analysis. The administrative server 250 and storage device 255can further be communicatively coupled to an analysis server 260 whichcan apply optimization and treatment algorithms to determine a suitablean optimized treatment protocol. This information can then be conveyedback the transdermal delivery device 270 via the network 210 to providethe patient with optimal treatment protocols. While a preferredembodiment envisions the use of mobile devices 230 as a means by whichto collect user data including the occurrence and onset of a craving,the system is equally capably of gaining such information by a user'sinterface with a personal computer 240 or the like. Indeed the device270 itself can be equipped with certain physiological sensors to recordphysical parameters of the user that may be later correlated with theefficacy of the treatment protocol and report these candidates to acentral server.

While one embodiment of the present invention comprises a digitalapplication resident and executable on a device such as a smart phone,PDA, cellular phone, or the like, one of reasonable skill in therelevant art will recognize that a separate data collection device canalso be utilized to memorialize the applicable data and indeed beincorporated into the bio-synchronous drug delivery system of thepresent invention. Such a device, regardless of form, generallycomprises a central processing unit(s) (CPU) or processor(s) coupled toa random-access memory (RAM), a read-only memory (ROM), a keyboard oruser interface, and a display or video adapter connected to a displaydevice. These devices may also optionally include a removable (mass)storage device (e.g., floppy disk, CD-ROM, CD-R, CD-RW, DVD, or thelike), a fixed (mass) storage device (e.g., hard disk), a communication(COMM) port(s) or interface(s), a modem, and a network interface card(NIC) or controller (e.g., Ethernet, transceiver).

In such a system the CPU communicates with other components of thesystem via a bi-directional system bus (including any necessaryinput/output (I/O) controller circuitry and other “glue” logic). Thebus, which includes address lines for addressing system memory, providesdata transfer between and among the various components. Random-accessmemory serves as the working memory for the CPU. The read-only memory(ROM) contains the basic input/output system code (BIOS)—a set oflow-level routines in the ROM that application programs and theoperating systems can use to interact with the hardware, includingreading characters from a user interface such as a keyboard, oroutputting characters to printers, and so forth.

Mass storage devices provide persistent storage on fixed and removablemedia, such as magnetic, optical, or magnetic-optical storage systems,flash memory, or any other available mass storage technology. The massstorage may be shared on a network, or it may be a dedicated massstorage. The fixed storage typically stores a body of program and datafor directing operation of the computer system, including an operatingsystem, user application programs, driver and other support files, aswell as other data files of all sorts.

In basic operation, program logic (including that which implementsmethodology of the present invention) is loaded from the removablestorage or fixed storage into the main (RAM) memory, for execution by aCPU. During operation of the program logic, the system accepts userinput from various forms of a user interface such as touch screen orkeyboard. In this manner, these input devices support manual user inputfor any process running on the system.

It is also contemplated that such a drug delivery system used inconjunction with the present invention can communicate with otherdevices (e.g., other computers, smart phone, PDA) wirelessly via anetwork interface card (NIC) connected to a network (e.g., Ethernetnetwork, Bluetooth wireless network, or the like). The system may alsocommunicate with local occasionally-connected devices (e.g., serialcable-linked devices) via the communication (COMM) interface, which mayinclude a RS-232 serial port, a Universal Serial Bus (USB) interface, orthe like. Devices that will be commonly connected locally to theinterface include laptop computers, handheld organizers, smart phonesand the like.

Regardless of the form of the device, the processors or internalprocessing capability will be capable of executing instructions embodiedas software to collect, synthesize, and manipulate data so as to producean optimal dosage protocol that can be transferred to, or by, abioactive agent application device and to collect and convey compliancedata regarding such treatment. The software programming code may beembodied on any of a variety of known media for use with a dataprocessing system. It also may be distributed on such media, or may bedistributed from the memory or storage of one computer system over anetwork of some type to other computer systems for use by such othersystems. Alternatively, the programming code may be embodied in thememory of the device and accessed by a microprocessor using an internalbus or embodied as firmware or a combination of firmware and software.The processes embodied as software generally comprise program modulesthat include routines, objects, components, data structures and the likethat perform particular tasks or implement particular abstract datatypes. The techniques and methods for embodying software programmingcode in memory, on physical media, and/or distributing software code vianetworks are well known and will not be further discussed herein. Onekey aspect of the present invention is the ability to provide nearreal-time emotional or psychological support to a user in conjunctionwith the use of the bio-synchronous bioactive agent delivery system.Support groups provide emotional counseling to assist patients duringperiods of intense emotional distress. Emotional support can be providedin the form of a phone call, voice mail, text message, email or thelike. According to one embodiment of the present invention the bioactiveagent delivery system can integrate one or more support features bywhich a user can gain emotional support. For example, upon experiencingan intense craving for nicotine the patient can communicate theexperience to a counselor via a user interface associated with thepresent invention. As the system or the present invention works toprovide the patient with emotional support it can also determine, basedon the user profile and collected compliance data, whether an immediatebolus of additional medication is warranted. If so, the counselor ormedical practitioner can remotely initiate the application of additionalmedication as emotional support is being administered. Similarlyemotional support can be immediately offered without additionalmedication.

In other embodiments, the temporal application of medication through thebioactive agent delivery system can be supplemented by the presentationof proactive supportive emails, texts and the like. For example a userimplementing the bioactive agent delivery system of the presentinvention that normally experiences a craving to smoke in the morningafter awakening will receive medication to relieve that desire shortlybefore arising. Supplementing the medication can be a proactive text,email or phone call to further support the patient's non-use of theaddictive substance.

FIG. 3 is a high level flowchart of a methodology by which abio-synchronous bioactive agent delivery device of the present inventioncan collect data with respect to treatment protocol compliance as wellas psychological and physiological factors and apply a suitabletreatment protocol. Such an exemplary process begins 305 with theinitiation 310 of a bio-synchronous transdermal treatment protocol usinga bioactive agent delivery device. Initially the bioactive agentdelivery device is programmed to deliver predetermined dosages of aparticular drug according to a temporal plan as determined by anattending physician or clinical expert. These predetermined treatmentsmay be formed by a user responding to a series of inquires to determinethe scope of the treatment and its initial temporal application. Forexample, the physician may gain information with respect to thepatient's physical attributes such as the patient's age, gender andweight as well as historical data with respect to the particular illnessbeing treated. Environmental factors can be considered as can thepatient's typical schedule. A wide variety of information can be gainedto enable the physician through use of one or more algorithms todetermine an initial, and later optimal treatment protocol. Oncedetermined that initial treatment protocol can be programmed into thetransdermal treatment device and initiated by the user aid then lateroptimized by using newly gained information.

Once the treatment protocol is initiated 310 the bioactive agentdelivery device not only applies the appropriate dosages at thepredetermined intervals but records data associated with each treatmentevent 315. For example, in one embodiment, the device of the presentinvention can sense its proximity to a user's epidermis and uponapplication of the treatment record and report successful compliancewith the treatment protocol. Similarly, if the device is no longer incontact with the user's epidermis and the treatment protocol indicates adosage is due, the device can record a non-compliant treatment protocolevent.

These recorded events can, along with additional information, betransmitted 320 to a data analysis module for further consideration. Inone embodiment the bioactive agent delivery device possesses a wirelesstransmitter that can directly interact with a network environment suchas the Internet to affect such transference of data. In otherembodiments, the bioactive agent deliver device can wirelessly (orserially) couple with a cell phone, PDA or the like via Bluetooth orsimilar short range wireless data connection technology to convey thedata which can then be processed locally or relayed to an analysismodule for consideration.

Once the data is collected and reported the analysis module, in oneembodiment of the present invention, can determine whether the collectedevent data indicates treatment protocol compliance 330. When the inquiryas to compliance indicates that the patient has followed the initialtreatment protocols the system may further seek to determine whether anypsychological events correlate 335 with the applications of theprescribed treatments. Psychological events can include such things asthe recordation of an intense craving or similar symptom. Thus despitethe patient's compliance with the treatment protocol, the patient'sreport of an ongoing problem may indicate evidence of an ineffectualtreatment protocol. Conversely, the lack of any emotional eventscorrelated with compliance with the treatment protocols may enable thesystem to conclude that the current treatment protocol should bemaintained 340.

One additional aspect of the bio-synchronous bioactive agent deliverydevice of the present invention is the ability to self-administer abolus 345 of a particular treatment drug. For example, a drug reservoirof the bioactive agent delivery device may possess sufficient capacitythat even with full compliance with the prescribed treatment protocols areserve of the prescribed drug is present to enable the user to safelyprescribe a one-time bolus. The present invention records such an eventand correlates it with both compliance data and any psychological inputsto address the efficacy of the treatment protocol. Thus even if thepatient reported an intense craving but nonetheless did not availthemself to a bolus, the system may elect to maintain 340 the currentprotocol of treatments.

However, when data indicates that the patient has complied 330 with thepredetermined treatment protocols, and registered a psychological event350 such as an intense craving and self-initiated 345 a bolus of theprescribed drug, an inquiry may be begun 350 as to whether the treatmentprotocol should be modified.

Using collected data, the analysis module determines whether theexisting treatment protocol should be modified. While the analysis maydetermine that the current protocol is to be maintained 340 the presentinvention, based on collected data, may move to modify 355 the currenttreatment protocol to increase the patient's opportunity for success.Modifications can include adjusting the temporal application of thedrug, modifying the amount of dosage and even modifying the type ofdrug. For example, the system may determine that the current applicationof a particular dose should occur 30 minutes earlier to counter thepatient's registration of an intense craving to smoke early in themorning. After applying the modification to the device and continuing tocollect data the system may once again modify the protocol but this timeincrease the dosage of the prescribed drug. These modifications can bepredetermined, directed by a health care provider, automated or anycombination thereof so as to arrive at an optimized treatment protocol.

The methodology shown in FIG. 3 can also report that the patient hasbeen non-complaint with the prescribed treatment protocol. Again thesystem can determine whether the patient has recorded a psychologicalevent 360 such as a craving or whether the user has initiated a bolostreatment 365.

Using this information the analysis module can again determine whether amodification 345 to the treatment protocol is warranted. In oneembodiment of the present invention the response to a non-compliance ofthe prescribed treatment protocol can be to maintain the protocol and toencourage compliance by offering emotional support 370. Similarly if thepatient self-initiated a bolus 365 the system can use the information anadditional application of the treatment drug (although non-complaint) todetermine whether the treatment protocol should be modified 350.

The process shown in FIG. 3 further indicates, according to oneembodiment of the present invention, the ability to combinephysiological support for the treatment of an ailment with pharmacology(via the bio-synchronous bioactive agent delivery device) withpsychological/emotional support. The initiation of 370 emotionaltreatment protocol support can be triggered by multiple events, and inother embodiments be proactively initiated to hopefully prevent theoccurrence of non-compliance or a psychological event.

For example, upon a user indicating that a craving is occurring, thepresent invention can record the psychological event for use indetermination of whether the treatment protocols should be modified, aswell as initiate emotional support to assist the user in overcoming thechallenge. A patient may find, despite compliance with the treatmentprotocol that a continuing craving is occurring. While the system maymodify the protocol for future treatments, immediate support can beconveyed to the patient to remain compliant with the plan, and in thecase of smoking cessation treatment, not smoke or, if necessary, toadminister a bolus of the prescribed drug to assist in not smoking.

Likewise, a report of non-compliance can trigger emotional support inthe form of a message to encourage the patient to comply with thetreatment protocol or directly interact with support personal. Forexample, these reports can in one embodiment, be automated, while inother embodiments of the present invention, involve the interaction of ahealthcare provider or a support group so a to provide individualizedand personal contact with the patient.

One of reasonable skill in the applicable art will recognize that thepresent invention is especially adept to assist the treatment ofaddiction. Indeed one contemplated application of the innovations of thepresent invention includes the treatment for cessation of nicotineaddiction. Prior approaches regarding nicotine replacement therapiesinclude a variety of protocols and treatment regimens to aid the user insmoking cessation. Many of the decision trees or adaptive treatmentstrategies clarify decision rules, indicate how to integrate differenttreatment regimens, and provide recommendations on how to use or applyvarious nicotine replacement drugs. However, none of the prior artregiments or protocols provides any integration, or optimization for anindividual patient, or the inclusion of emotional support. In manycases, an attending physician provides such optimization or treatmentsuggestions, but these suggestions or recommendation are not timelyapplied. One embodiment of the present invention is to utilize collecteddata, and user profile information to establish pharmacology andaddiction cessation treatment regimens that implement an optimal drugdelivery protocol to the bioactive agent delivery device that can bemodified on a near real-time basis, with additional emotional support.

One feature of the present invention is the ability to continuallymonitor, modify and optimize the treatment regimen. As one of reasonableskill in the relevant art will appreciate, there are numerous smokingcessation protocols available to clinicians and physicians to aid in thedevelopment of a smoking (or addictive drug) cessation program.According to one embodiment of the present invention, a system isimplemented to collect data regarding addictive cravings as well asother information such as compliance that can be used to determine anappropriate integrated and optimized treatment regimen. While individualdata regarding the user's is an important aspect in determining thecorrect dosage of cessation assisting drugs, other information withrespect to each individual must and can be gathered and applied toarrive at an optimal dosage delivery program. The present invention notonly collects data with respect to the time, duration, and intensity ofcraving but also information with respect to the individual state ofmind, and environmental factors that may have significant impact on thesuccess of the drug delivery protocol.

The present invention thus collects a wide variety and range of datafrom an actual smoker or disease sufferer and determines and implementsan optimal drug delivery protocol. This optimal drug delivery protocolcan thereafter be transferred, either wirelessly or serially, to abioactive agent delivery device. Included in this calculation is thisdetermination, for this particular user, what the optimal transdermalflux rate and nicotine (drug) plasma concentration should be. Byproducing such information the bioactive agent delivery device candeliver to this user the optimal amount and temporal application of theappropriate drug.

FIG. 4 is, according to one embodiment of the present invention, a highlevel flow chart of a methodology to determine and to optimize anaddictive drug cessation program using a bioactive agent deliverydevice. The process begins 405 by establishing a user profile 410. Theuser profile, as discussed herein, includes various personal data withrespect to the individualized user as well as historical addictive data.Once a user profile has been established the user can indicate 420 theirlevel of motivation to be free of their symptoms or addictivetendencies. This combined with their prior symptoms/addictive habits 430can establish an initial treatment protocol 440 that can be thereaftertransmitted 4450 to the bioactive agent delivery device. Using thisinitial treatment protocol the bioactive agent delivery device canprovide established and predetermined delivery of the cessation drugs toaid the user in terminating his or her addictive behavior. (Otherclasses of drugs can also be used based on the condition being treated)

After the initial implementation, the system continues to collect 450real-time temporal data regarding the user's symptoms or cravings anddesires for the addictive item. For example with respect to smokingcessation, every time a smoker feels the need to have a cigarette theuser can input that craving into the data collection application thatcan be used to validate or modify 460 existing cessation treatmentprotocols. Based on the data received from the user regarding theircravings and desires engaging and addictive behavior, the treatmentprotocol can be adjusted to provide either more or less cessation drugsas required. The new modified instructions or protocols can again bedownloaded 470 to the bioactive agent delivery device for immediateimplementation by the user. This process is iterative, STET continualand ends when the users is free for the symptoms of the disease i.e. thedesire to smoke.

As the treatment protocol is being refined through the collection ofdata, the present invention can both proactively and reactively providethe patient with emotional treatment support 480. As a user indicatesthe existence of a craving or other symptom, the system can respond witha message via text or phone encouraging the user to maintain his or herconviction to the treatment protocol. Similarly, after recognizing thata patient is likely to experience a craving at a particular time of day,the system can proactively provide emotional support to once againmaintain the program.

To better understand the novel features of the present inventionconsider the following example in view of FIG. 5. FIG. 5 presents onemethod embodiment for optimized bio-synchronous drug delivery. Inaccordance with the method shown in FIG. 5, assume an individual who hassmoked consistently for several years wishes to stop smoking Thatindividual is a male, approximately 40 years old, weighs 190 pounds, andcurrently smokes on average one pack of cigarettes per day. Thisindividual's current choice of cigarettes contains approximately 8 mg ofnicotine per cigarette. This user typically smokes two cigarettes in themorning after arising at 6:00 AM, two or three cigarettes near or duringlunch, and then two or three cigarettes after dinner (approximately 7:00PM) before retiring for the evening. The individual has also indicatedthat he wishes to quit smoking within the next 30 days.

To ease this individual's desire for a cigarette he has elected to use abioactive agent delivery device which can automatically provide acertain amount of nicotine at certain times throughout the day. Inaddition, and according to one embodiment of the present invention, thisbioactive agent delivery device is linked to the system embodied as thepresent invention that optimizes the drug delivery protocol based on hisindividual characteristics, temporal environment, history, and desire toquit smoking.

After inputting the initial data into the system the drug deliveryoptimization system identifies and establishes 510 a specific protocoland drug cessation program that would most likely result in hiscessation of smoking within 30 days. This protocol is uploaded to thebioactive agent delivery device so as to provide nicotine or othersmoking cessation drugs at key points throughout the day, and to aid inhis ability to resist the temptation to smoke. The program is initiated520. As he wears the drug delivery device he interacts with the drugdelivery optimization application to key in data with respect tocravings or desires to smoke a cigarette. As data is collected 530, andis processed (analyzed) 540, a new optimize drug delivery protocol isdeveloped and delivered to the device. Additionally, the individualreceives a combination of emails, texts, and voicemails encouraging hiscontinued compliance with the program. These emotionally supportivemessages may be proactive, reactive, or both. New (modified) drugdelivery protocols are compared 550 to the existing drug deliveryprotocol currently in place in the bioactive agent delivery device. Whenthe new drug delivery protocol substantively differs from the existingprotocol the bioactive agent delivery device is updated 560 so as toprovide the user with an improved and ideally optimal delivery ofcessation aiding drugs.

For example, assume that every morning as the individual arises he has astrong desire to smoke a cigarette. The initial application of drugs hasnot effectively curtailed that desire. Therefore, immediately uponwaking up the individual accesses the drug delivery optimization programon his smart phone or PDA and indicates his strong desire to have acigarette. He may self-initiate a bolus of nicotine to overcome thedesire to smoke. If he indeed does have a cigarette that data isinputted as well. Along with a measure of intensity of the desire, theprogram collects data with respect to when this particular cravingoccurred and correlates this event with other events in the past. Ifover a certain period of time the user consistently craves a cigarettebetween 7 AM and 7:30 AM, the application can modify the drug deliveryprotocol to provide increased nicotine supplements at an appointed timeprior to 7 AM so as to prevent the craving. Moreover, at approximately7:00 AM the user will receive an automated message encouraging him notto smoke. Similarly, if the user indicates that in the evening after alarge meal he has no desire to smoke a cigarette yet after having adrink on Friday the craving returns, the drug delivery optimizationprogram may determine that on Fridays from 4 to 6 PM a supplementaldelivery of nicotine may be required to prevent a smoking event. In thismanner the historical data input by the user is analyzed and used tooptimize the dosage and delivery time of the transdermal drug.

In other embodiments of the present invention, the bioactive agentdelivery device itself can be used to collect data and to modify its ownprogramming while in other embodiments these modifications aredetermined remotely.

As will be understood by those familiar with the art, the invention maybe embodied in other specific forms without departing from the spirit oressential characteristics thereof. Likewise, the particular naming anddivision of the modules, managers, functions, systems, engines, layers,features, attributes, methodologies, and other aspects are not mandatoryor significant, and the mechanisms that implement the invention or itsfeatures may have different names, divisions, and/or formats.Furthermore, as will be apparent to one of ordinary skill in therelevant art, the modules, managers, functions, systems, engines,layers, features, attributes, methodologies, and other aspects of theinvention can be implemented as software, hardware, firmware, or anycombination of the three. Of course, wherever a component of the presentinvention is implemented as software, the component can be implementedas a script, as a standalone program, as part of a larger program, as aplurality of separate scripts and/or programs, as a statically ordynamically linked library, as a kernel loadable module, as a devicedriver, and/or in every and any other way known now or in the future tothose of skill in the art of computer programming. Additionally, thepresent invention is in no way limited to implementation in any specificprogramming language, or for any specific operating system orenvironment

It is to be clearly understood that the foregoing description is madeonly by way of example and not as a limitation to the scope of theinvention. Particularly, it is recognized that the teachings of theforegoing disclosure will suggest other modifications to those personsskilled in the relevant art. Such modifications may involve otherfeatures that are already known per se and which may be used instead ofor in addition to features already described herein. Although claimshave been formulated in this application to particular combinations offeatures, it should be understood that the scope of the disclosureherein also includes any novel feature or any novel combination offeatures disclosed either explicitly or implicitly or any generalizationor modification thereof which would be apparent to persons skilled inthe relevant art, whether or not such relates to the same invention aspresently claimed in any claim and whether or not it mitigates any orall of the same technical problems as confronted by the presentinvention. The Applicant hereby reserves the right to formulate newclaims to such features and/or combinations of such features during theprosecution of the present application or of any further applicationderived therefrom.

1. A method for optimized bio-synchronous drug delivery, the methodcomprising: establishing a bio-synchronous treatment protocol;initiating the bio-synchronous treatment protocol wherein thebio-synchronous treatment protocol includes use of a bio-synchronousbioactive agent delivery device; gathering patient data during thebio-synchronous treatment protocol; analyzing gathered patient data;determining based on gathered patient data whether modification to thebio-synchronous treatment protocol is required; and responsive todetermining modification to the bio-synchronous treatment protocol isrequired, modifying the bio-synchronous treatment protocol and use ofthe bio-synchronous bioactive agent delivery device.
 2. The method foroptimized bio-synchronous drug delivery according to claim 1, whereinthe bio-synchronous treatment protocol includes temporal administrationof pharmacological elements based on individual patient temporalpatterns.
 3. The method for optimized bio-synchronous drug deliveryaccording to claim 1, wherein the bio-synchronous treatment protocolincludes temporal administration of pharmacological elements based onpatient innately rhythmic biological processes.
 4. The method foroptimized bio-synchronous drug delivery according to claim 1, whereinthe bio-synchronous treatment protocol includes temporal administrationof pharmacological elements based on a combination of individual patienttemporal patterns and patient innately rhythmic biological processes. 5.The method for optimized bio-synchronous drug delivery according toclaim 1, wherein the bio-synchronous treatment protocol includestemporal psychological support.
 6. The method for optimizedbio-synchronous drug delivery according to claim 5, wherein temporalpsychological support is linked to patient temporal patterns.
 7. Themethod for optimized bio-synchronous drug delivery according to claim 5,wherein temporal psychological support is linked to patient innatelyrhythmic biological processes.
 8. The method for optimizedbio-synchronous drug delivery according to claim 5, wherein temporalpsychological support is proactively based on the bio-synchronoustreatment protocol.
 9. The method for optimized bio-synchronous drugdelivery according to claim 8, wherein temporal psychological supportincludes an electronic message.
 10. The method for optimizedbio-synchronous drug delivery according to claim 8, wherein temporalpsychological support includes direct interaction with psychologicalsupport personnel.
 11. The method for optimized bio-synchronous drugdelivery according to claim 1, wherein the bio-synchronous bioactiveagent delivery device administers pharmacological elements based onindividual patient temporal patterns.
 12. The method for optimizedbio-synchronous drug delivery according to claim 1, wherein thebio-synchronous bioactive agent delivery device administerspharmacological elements based on innately rhythmic biologicalprocesses.
 13. The method for optimized bio-synchronous drug deliveryaccording to claim 1, wherein patient data includes compliance with thebio-synchronous treatment protocol.
 14. The method for optimizedbio-synchronous drug delivery according to claim 1, wherein patient dataincludes patient physiological data.
 15. The method for optimizedbio-synchronous drug delivery according to claim 1, wherein patient dataincludes patient psychological data.
 16. The method for optimizedbio-synchronous drug delivery according to claim 15, wherein patientpsychological data includes a patient reported emotion.
 17. The methodfor optimized bio-synchronous drug delivery according to claim 16,wherein temporal psychological support is reactive based on the patientreported emotion.
 18. The method for optimized bio-synchronous drugdelivery according to claim 17, wherein temporal psychological supportincludes an electronic message.
 19. The method for optimizedbio-synchronous drug delivery according to claim 17, wherein temporalpsychological support includes direct interaction with psychologicalsupport personnel.
 20. The method for optimized bio-synchronous drugdelivery according to claim 16, wherein the patient reported emotionincludes a craving.
 21. The method for optimized bio-synchronous drugdelivery according to claim 16, wherein the patient reported emotionincludes anxiety.
 22. The method for optimized bio-synchronous drugdelivery according to claim 1, wherein modifying includes remotelyadjusting the bio-synchronous treatment protocol associated with thebio-synchronous bioactive agent delivery device.
 23. The method foroptimized bio-synchronous drug delivery according to claim 1, whereinthe bio-synchronous bioactive agent delivery device initiates diffusionof a bioactive agent through the epidermis is assisted using one or morefrom the group consisting of micro-needles, iontophoresis, sonophoresis,electroporation, nanoporation, dermal abrasion, sub cutaneous delivery,heat, piezoelectric droplet jet dispensers, thermal droplet jetdispensers, and light and chemical permeation enhancers.
 24. The methodfor optimized bio-synchronous drug delivery according to claim 23,wherein the at least one bioactive agent is chosen from the groupconsisting of alprazolam, apomorphine, azelastine, buprenorphine,bupropion, clonidine, enalpril, estradiol, ethinyl estradiol, fentanyl,granisetron, insulin, lidocaine, memantine, methylphenidate,methamphetamine, nitroglycerine, nicotine, norethisterone acetate(NETA), norelgestromine, oxybutynin, pergolide, phenteramine,pramipexole, ramipril, ropinirole, rotigotine, scopolamine, selegiline,tecrine, testosterone, timolol and tolterodine.
 25. A method foroptimized bio-synchronous drug delivery of a bio-synchronous treatmentprotocol, the method comprising: collecting patient data during use of abio-synchronous bioactive agent delivery device according to thebio-synchronous treatment protocol; analyzing collected patient dataduring use of the bio-synchronous bioactive agent delivery device; andmodifying, during use of the bio-synchronous bioactive agent deliverydevice, the bio-synchronous treatment protocol.
 26. The method foroptimized bio-synchronous drug delivery according to claim 25, whereinthe bio-synchronous treatment protocol includes administration of one ormore pharmacological elements using the bio-synchronous bioactive agentdelivery device and providing psychological support.
 27. The method foroptimized bio-synchronous drug delivery according to claim 26, whereinthe bio-synchronous treatment protocol includes temporal administrationof pharmacological elements based on individual patient temporalpatterns.
 28. The method for optimized bio-synchronous drug deliveryaccording to claim 26, wherein the bio-synchronous treatment protocolincludes temporal administration of pharmacological elements based onpatient innately rhythmic biological processes.
 29. The method foroptimized bio-synchronous drug delivery according to claim 26, whereinthe bio-synchronous treatment protocol includes temporal administrationof pharmacological elements based on a combination of individual patienttemporal patterns and patient innately rhythmic biological processes.30. The method for optimized bio-synchronous drug delivery according toclaim 26, wherein psychological support is reactive based on collectedpatient data.
 31. The method for optimized bio-synchronous drug deliveryaccording to claim 26, wherein psychological support is linked toindividual patient temporal patterns.
 32. The method for optimizedbio-synchronous drug delivery according to claim 26, whereinpsychological support is linked to innately rhythmic biologicalprocesses.
 33. The method for optimized bio-synchronous drug deliveryaccording to claim 26, wherein psychological support is proactive basedon the bio-synchronous treatment protocol.
 34. The method for optimizedbio-synchronous drug delivery according to claim 26, whereinpsychological support includes an electronic message.
 35. The method foroptimized bio-synchronous drug delivery according to claim 26, whereinpsychological support includes direct interaction with psychologicalsupport personnel.
 36. The method for optimized bio-synchronous drugdelivery according to claim 25, wherein patient data includes patientemotional state data.
 37. The method for optimized bio-synchronous drugdelivery according to claim 36, wherein patient emotional state dataincludes cravings.
 38. The method for optimized bio-synchronous drugdelivery according to claim 36, wherein patient emotional state dataincludes anxiety.
 39. The method for optimized bio-synchronous drugdelivery according to claim 36, wherein collecting includes gatheringcompliance data regarding patient compliance of the bio-synchronoustreatment protocol and use of the bio-synchronous bioactive agentdelivery device.
 40. The method for optimized bio-synchronous drugdelivery according to claim 39, wherein analyzing includes correlatingcompliance data with patient emotional state data.
 41. The method foroptimized bio-synchronous drug delivery according to claim 25, whereinpatient data includes patient physiological data.
 42. The method foroptimized bio-synchronous drug delivery according to claim 25, whereinmodifying includes initiating temporal psychological support.
 43. Themethod for optimized bio-synchronous drug delivery according to claim25, wherein modifying includes adjusting temporal administration ofpharmacological elements by the bio-synchronous bioactive agent deliverydevice.
 44. The method for optimized bio-synchronous drug deliveryaccording to claim 25, wherein the bio-synchronous bioactive agentdelivery device initiates diffusion of a bioactive agent through theepidermis is assisted using one or more from the group consisting ofmicro-needles, iontophoresis, sonophoresis, electroporation,nanoporation, dermal abrasion, sub cutaneous delivery, heat,piezoelectric droplet jet dispensers, thermal droplet jet dispensers,and light and chemical permeation enhancers.
 45. The method foroptimized bio-synchronous drug delivery according to claim 44, whereinthe at least one bioactive agent is chosen from the group consisting ofalprazolam, apomorphine, azelastine, buprenorphine, bupropion,clonidine, enalpril, estradiol, ethinyl estradiol, fentanyl,granisetron, insulin, lidocaine, memantine, methylphenidate,methamphetamine, nitroglycerine, nicotine, norethisterone acetate(NETA), norelgestromine, oxybutynin, pergolide, phenteramine,pramipexole, ramipril, ropinirole, rotigotine, scopolamine, selegiline,tecrine, testosterone, timolol and tolterodine.
 46. A system foroptimized bio-synchronous drug delivery, comprising a bio-synchronoustreatment protocol; a bio-synchronous bioactive agent delivery deviceconfigured to administer pharmacological elements based on thebio-synchronous treatment protocol; patient data gathered duringadministration of the bio-synchronous treatment protocol; and ananalysis module operable to analyze gathered patient data and optimizethe bio-synchronous treatment protocol.
 47. The system for optimizedbio-synchronous drug delivery according to claim 46, wherein theanalysis module is operable to create a modified bio-synchronoustreatment protocol based on gathered patient data.
 48. The system foroptimized bio-synchronous drug delivery according to claim 47, furthercomprising a communication module operable to communicate the modifiedbio-synchronous treatment protocol to the bioactive agent deliverydevice.
 49. The system for optimized bio-synchronous drug deliveryaccording to claim 46, wherein the bio-synchronous treatment protocolincludes pharmacological elements temporally administered based onindividual patient temporal patterns.
 50. The system for optimizedbio-synchronous drug delivery according to claim 46, wherein thebio-synchronous treatment protocol includes pharmacological elementstemporally administered based on patient innately rhythmic biologicalprocesses.
 51. The system for optimized bio-synchronous drug deliveryaccording to claim 46, wherein the bio-synchronous treatment protocolincludes pharmacological elements temporally administered based on acombination of individual patient temporal patterns and patient innatelyrhythmic biological processes
 52. The system for optimizedbio-synchronous drug delivery according to claim 46, wherein thebio-synchronous treatment protocol includes temporal psychologicalsupport.
 53. The system for optimized bio-synchronous drug deliveryaccording to claim 52, wherein temporal psychological support is linkedto patient temporal patterns.
 54. The system for optimizedbio-synchronous drug delivery according to claim 52, wherein temporalpsychological support is linked to patient innately rhythmic biologicalprocesses.
 55. The system for optimized bio-synchronous drug deliveryaccording to claim 52, wherein temporal psychological support isproactively initiated on the bio-synchronous treatment protocol.
 56. Thesystem for optimized bio-synchronous drug delivery according to claim55, wherein temporal psychological support includes an electronicmessage.
 57. The system for optimized bio-synchronous drug deliveryaccording to claim 55, wherein temporal psychological support includesdirect interaction with psychological support personnel.
 58. The systemfor optimized bio-synchronous drug delivery according to claim 46,wherein the bio-synchronous bioactive agent delivery device administerspharmacological elements based on individual patient temporal patterns.59. The system for optimized bio-synchronous drug delivery according toclaim 46, wherein the bio-synchronous bioactive agent delivery deviceadministers pharmacological elements based on innately rhythmicbiological processes.
 60. The system for optimized bio-synchronous drugdelivery according to claim 46, wherein the bio-synchronous bioactiveagent delivery device administers pharmacological elements based oninnately rhythmic biological processes and on individual patienttemporal patterns.
 61. The system for optimized bio-synchronous drugdelivery according to claim 46, wherein patient data includes compliancedata reflecting compliance with the bio-synchronous treatment protocol.62. The system for optimized bio-synchronous drug delivery according toclaim 46, wherein patient data includes patient physiological data. 63.The system for optimized bio-synchronous drug delivery according toclaim 46, wherein patient data includes patient psychological data. 64.The system for optimized bio-synchronous drug delivery according toclaim 63, wherein patient psychological data includes a patient reportedemotion.
 65. The system for optimized bio-synchronous drug deliveryaccording to claim 64, wherein temporal psychological support isreactive based on the patient reported emotion.
 66. The system foroptimized bio-synchronous drug delivery according to claim 65, whereintemporal psychological support includes an electronic message.
 67. Thesystem of optimized bio-synchronous drug delivery according to claim 65,wherein temporal psychological support includes direct interaction withpsychological support personnel.
 68. The system for optimizedbio-synchronous drug delivery according to claim 64, wherein the patientreported emotion includes a craving.
 69. The system for optimizedbio-synchronous drug delivery according to claim 64, wherein the patientreported emotion includes anxiety.
 70. The system for optimizedbio-synchronous drug delivery according to claim 46, wherein thebio-synchronous bioactive agent delivery device initiates diffusion of abioactive agent through the epidermis is assisted using one or more fromthe group consisting of micro-needles, iontophoresis, sonophoresis,electroporation, nanoporation, dermal abrasion, sub cutaneous delivery,heat, piezoelectric droplet jet dispensers, thermal droplet jetdispensers, and light and chemical permeation enhancers.
 71. The systemfor optimized bio-synchronous drug delivery according to claim 70,wherein the at least one bioactive agent is chosen from the groupconsisting of alprazolam, apomorphine, azelastine, buprenorphine,bupropion, clonidine, enalpril, estradiol, ethinyl estradiol, fentanyl,granisetron, insulin, lidocaine, memantine, methylphenidate,methamphetamine, nitroglycerine, nicotine, norethisterone acetate(NETA), norelgestromine, oxybutynin, pergolide, phenteramine,pramipexole, ramipril, ropinirole, rotigotine, scopolamine, selegiline,tecrine, testosterone, timolol and tolterodine.